Anna Szylling, Filip Raciborski, Oksana Wojas, Konrad Furmańczyk, Edyta Krzych-Fałta, Jean Bousquet, Boleslaw Samoliński
Background
Allergic diseases—rhinitis and asthma—are the most common chronic conditions affecting adults. Traditional approaches to allergy diagnosis and treatment do not meet the health needs of all patients. Treatment adherence remains a challenge for physicians. The ubiquity of Internet access paired with limited in-person contact with medical personnel in the course of the COVID-19 pandemic demonstrated the potential of mHealth in communicating health information.
Body
The abundance of new applications dedicated to various medical specialties encourages reflection on the informed use of such tools. The paper takes a closer look at the potential of mHealth and presents conclusions of selected studies focusing on the use of good apps. The strength weakness opportunities threats analysis was used to illustrate the strengths of the mHealth strategy, as well as its advantages, limitations and areas in need of further development.
Conclusion
The strength of mHealth depends on the quality and quantity of the collected patient data, its reliable processing, as well as publication of outcomes and conclusions from analyses. Therefore, it is necessary to promote the use of validated applications among patients, physicians and medical staff.
{"title":"Why the role of mHealth in allergy diagnosis and treatment adherence cannot be overlooked","authors":"Anna Szylling, Filip Raciborski, Oksana Wojas, Konrad Furmańczyk, Edyta Krzych-Fałta, Jean Bousquet, Boleslaw Samoliński","doi":"10.1002/clt2.12298","DOIUrl":"https://doi.org/10.1002/clt2.12298","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Allergic diseases—rhinitis and asthma—are the most common chronic conditions affecting adults. Traditional approaches to allergy diagnosis and treatment do not meet the health needs of all patients. Treatment adherence remains a challenge for physicians. The ubiquity of Internet access paired with limited in-person contact with medical personnel in the course of the COVID-19 pandemic demonstrated the potential of mHealth in communicating health information.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Body</h3>\u0000 \u0000 <p>The abundance of new applications dedicated to various medical specialties encourages reflection on the informed use of such tools. The paper takes a closer look at the potential of mHealth and presents conclusions of selected studies focusing on the use of good apps. The strength weakness opportunities threats analysis was used to illustrate the strengths of the mHealth strategy, as well as its advantages, limitations and areas in need of further development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The strength of mHealth depends on the quality and quantity of the collected patient data, its reliable processing, as well as publication of outcomes and conclusions from analyses. Therefore, it is necessary to promote the use of validated applications among patients, physicians and medical staff.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12298","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50136690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adel H. Mansur, Julie Marsh, Ali Bahron, Maximillian Thomas, Gareth Walters, John Busby, Liam G. Heaney, Mamidipudi Thirumala Krishna
Background
House dust mite (HDM) is the most common sensitising allergen in asthma. Ethnic minority groups (EMGs) in the UK are more likely to live in deprived conditionings with a greater exposure to HDM and other aero-allergens.
Aim
To compare the ethnicity-based patterns of sensitisation to aero-allergens and the impact of ethnicity on clinical outcomes in patients with difficult-to-treat asthma (DTA).
Methods
Data of patients with DTA were extracted from the registry of the Birmingham Regional Severe Asthma Service (BRSAS), which have a catchment population of 7.3million from Central England. Patients from White and EMG backgrounds were compared in terms of the prevalence of atopy, total serum immunoglobulin E (IgE), specific serum IgE (ssIgE) and asthma related clinical outcomes. Logistic regression analysis was conducted to explore ethnicity-based risk factors for HDM sensitisation.
Results
A total of 1272 patients [White 1016 (79.9%), EMG 256 (20.1%) EMG] with a median age of 51 years (range 16–97) were included in the analysis. Patients from EMG were more likely (64%) to reside in the worst scale of index of multiple deprivation (IMD) than the White patients (25.5%), p < 0.0001. Positive HDM sensitisation was more prevalent in the EMG than in the White group [142/216 (66%) versus 375/842 (45%), p < 0.0001]. The median HDM ssIgE level was higher in the EMG than in the White group [3.0 KUA/L (IQR 0.06, 11.5) versus 0.1 (0.01, 3.0), p < 0.000001]. The odds ratio for positive sensitisation to HDM conveyed by the EMG status was 2.61 (95%CI, 1.8–3.8), p < 0.0001. Compared to the White group, the EMG had higher median total serum IgE [326 KU/L (115, 971) versus 114 (29.8, 434.8), p < 0.000001], higher blood eosinophil count (0.36 × 109(0.18, 0.62) versus 0.23 (0.1,0.47), p < 0.000001), were marginally more atopic (79.2% vs. 75.6%, p = 0.098) and were less likely to being on maintenance oral corticosteroids (22% vs. 39.7%, p < 0.0001).
Conclusion
In this DTA cohort, positive HDM sensitisation was greater amongst the EMG than the White patients. The EMG status was a significant risk factor for HDM sensitisation.
{"title":"Difficult-to-treat asthma patients from ethnic minority groups in central England are at an enhanced risk of house dust mite sensitisation","authors":"Adel H. Mansur, Julie Marsh, Ali Bahron, Maximillian Thomas, Gareth Walters, John Busby, Liam G. Heaney, Mamidipudi Thirumala Krishna","doi":"10.1002/clt2.12303","DOIUrl":"https://doi.org/10.1002/clt2.12303","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>House dust mite (HDM) is the most common sensitising allergen in asthma. Ethnic minority groups (EMGs) in the UK are more likely to live in deprived conditionings with a greater exposure to HDM and other aero-allergens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To compare the ethnicity-based patterns of sensitisation to aero-allergens and the impact of ethnicity on clinical outcomes in patients with difficult-to-treat asthma (DTA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data of patients with DTA were extracted from the registry of the Birmingham Regional Severe Asthma Service (BRSAS), which have a catchment population of 7.3million from Central England. Patients from White and EMG backgrounds were compared in terms of the prevalence of atopy, total serum immunoglobulin E (IgE), specific serum IgE (ssIgE) and asthma related clinical outcomes. Logistic regression analysis was conducted to explore ethnicity-based risk factors for HDM sensitisation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1272 patients [White 1016 (79.9%), EMG 256 (20.1%) EMG] with a median age of 51 years (range 16–97) were included in the analysis. Patients from EMG were more likely (64%) to reside in the worst scale of index of multiple deprivation (IMD) than the White patients (25.5%), <i>p</i> < 0.0001. Positive HDM sensitisation was more prevalent in the EMG than in the White group [142/216 (66%) versus 375/842 (45%), <i>p</i> < 0.0001]. The median HDM ssIgE level was higher in the EMG than in the White group [3.0 KUA/L (IQR 0.06, 11.5) versus 0.1 (0.01, 3.0), <i>p</i> < 0.000001]. The odds ratio for positive sensitisation to HDM conveyed by the EMG status was 2.61 (95%CI, 1.8–3.8), <i>p</i> < 0.0001. Compared to the White group, the EMG had higher median total serum IgE [326 KU/L (115, 971) versus 114 (29.8, 434.8), <i>p</i> < 0.000001], higher blood eosinophil count (0.36 × 10<sup>9</sup>(0.18, 0.62) versus 0.23 (0.1,0.47), <i>p</i> < 0.000001), were marginally more atopic (79.2% vs. 75.6%, <i>p</i> = 0.098) and were less likely to being on maintenance oral corticosteroids (22% vs. 39.7%, <i>p</i> < 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this DTA cohort, positive HDM sensitisation was greater amongst the EMG than the White patients. The EMG status was a significant risk factor for HDM sensitisation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50125539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jan Hubert, Susanne Vrtala, Bruno Sopko, Scot E. Dowd, Qixin He, Pavel B. Klimov, Karel Harant, Pavel Talacko, Tomas Erban
Background
The domestic mite Blomia tropicalis is a major source of allergens in tropical and subtropical regions. Despite its great medical importance, the allergome of this mite has not been sufficiently studied. Only 14 allergen groups have been identified in B. tropicalis thus far, even though early radioimmunoelectrophoresis techniques (27 uncharacterized allergen complexes) and comparative data based on 40 allergen groups officially recognized by the World Health Organization (WHO)/IUIS in domestic astigmatid mites suggest the presence of a large set of additional allergens.
Methods
Here, we employ a multiomics approach to assess the allergome of B. tropicalis using genomic and transcriptomic sequence data and perform highly sensitive protein abundance quantification.
Findings
Among the 14 known allergen groups, we confirmed 13 (one WHO/IUIS allergen, Blo t 19, was not found) and identified 16 potentially novel allergens based on sequence similarity. These data indicate that B. tropicalis shares 27 known/deduced allergen groups with pyroglyphid house dust mites (genus Dermatophagoides). Among these groups, five allergen-encoding genes are highly expressed at the transcript level: Blo t 1, Blo t 5, Blo t 21 (known), Blo t 15, and Blo t 18 (predicted). However, at the protein level, a different set of most abundant allergens was found: Blo t 2, 10, 11, 20 and 21 (mite bodies) or Blo t 3, 4, 6 and predicted Blo t 13, 14 and 36 (mite feces).
Interpretation
We report the use of an integrated omics method to identify and predict an array of mite allergens and advanced, label-free proteomics to determine allergen protein abundance. Our research identifies a large set of novel putative allergens and shows that the expression levels of allergen-encoding genes may not be strictly correlated with the actual allergenic protein abundance in mite bodies.
背景热带圆蚧是热带和亚热带地区的主要致敏源。尽管这种螨在医学上具有重要意义，但其致敏性尚未得到充分研究。到目前为止，在热带B.tropicalis中仅鉴定出14个过敏原组，尽管早期的放射免疫电泳技术（27种未表征的过敏原复合物）和基于40种由世界卫生组织（世界卫生组织）/IUIS正式认可的过敏原组的比较数据表明存在大量额外的过敏原。方法在这里，我们采用多组学方法，利用基因组和转录组序列数据评估热带双歧杆菌的致敏组，并进行高灵敏度的蛋白质丰度定量。结果在14个已知过敏原组中，我们确认了13个（未发现一个世界卫生组织/IUIS过敏原，Blo t 19），并根据序列相似性确定了16个潜在的新过敏原。这些数据表明热带B.tropicalis与焦纹屋尘螨（Dermachopoides属）共有27个已知/推断的过敏原组。在这些组中，有五个过敏原编码基因在转录物水平上高度表达：印迹1、印迹5、印迹21（已知）、印迹15和印迹18（预测）。然而，在蛋白质水平上，发现了一组不同的最丰富的过敏原：印迹2、10、11、20和21（螨体）或印迹3、4、6，并预测印迹13、14和36（螨粪）。解释我们报告了使用综合组学方法来识别和预测一系列螨类过敏原，并使用先进的无标记蛋白质组学来确定过敏原蛋白丰度。我们的研究确定了一大组新的假定过敏原，并表明过敏原编码基因的表达水平可能与螨体内实际的致敏蛋白丰度没有严格相关性。
{"title":"Predicting Blomia tropicalis allergens using a multiomics approach","authors":"Jan Hubert, Susanne Vrtala, Bruno Sopko, Scot E. Dowd, Qixin He, Pavel B. Klimov, Karel Harant, Pavel Talacko, Tomas Erban","doi":"10.1002/clt2.12302","DOIUrl":"https://doi.org/10.1002/clt2.12302","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The domestic mite <i>Blomia tropicalis</i> is a major source of allergens in tropical and subtropical regions. Despite its great medical importance, the allergome of this mite has not been sufficiently studied. Only 14 allergen groups have been identified in <i>B. tropicalis</i> thus far, even though early radioimmunoelectrophoresis techniques (27 uncharacterized allergen complexes) and comparative data based on 40 allergen groups officially recognized by the World Health Organization (WHO)/IUIS in domestic astigmatid mites suggest the presence of a large set of additional allergens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we employ a multiomics approach to assess the allergome of <i>B. tropicalis</i> using genomic and transcriptomic sequence data and perform highly sensitive protein abundance quantification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Among the 14 known allergen groups, we confirmed 13 (one WHO/IUIS allergen, Blo t 19, was not found) and identified 16 potentially novel allergens based on sequence similarity. These data indicate that <i>B. tropicalis</i> shares 27 known/deduced allergen groups with pyroglyphid house dust mites (genus <i>Dermatophagoides</i>). Among these groups, five allergen-encoding genes are highly expressed at the transcript level: Blo t 1, Blo t 5, Blo t 21 (known), Blo t 15, and Blo t 18 (predicted). However, at the protein level, a different set of most abundant allergens was found: Blo t 2, 10, 11, 20 and 21 (mite bodies) or Blo t 3, 4, 6 and predicted Blo t 13, 14 and 36 (mite feces).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>We report the use of an integrated omics method to identify and predict an array of mite allergens and advanced, label-free proteomics to determine allergen protein abundance. Our research identifies a large set of novel putative allergens and shows that the expression levels of allergen-encoding genes may not be strictly correlated with the actual allergenic protein abundance in mite bodies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50117356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael A. Portelli, Sangita Bhaker, Vincent Pang, David O. Bates, Simon R. Johnson, Andrew P. Mazar, Dominick Shaw, Christopher Brightling, Ian Sayers
Background
Expression of the urokinase plasminogen activator receptor (uPAR) is elevated in the airway epithelium in asthma; however, the contribution of uPAR to asthma pathogenesis and scope for therapeutic targeting remains unknown.
Objectives
To determine (i) the expression profile of uPAR in cultured human bronchial epithelial cells (HBEC) from asthma patients, (ii) the relationship between uPAR and the epithelial barrier, including blocking uPAR functions and (iii) the function of different uPAR isoforms.
Methods
uPAR levels in HBECs isolated from asthma patients and cells at air liquid interface (ALI) during differentiation were quantified. Transepithelial electrical resistance or electrical cell impedance sensing was used to relate uPAR levels to barrier properties, including effects of uPAR blocking antibodies. The functional effects of gain of function was determined using transcriptomics, in cells over-expressing membrane (muPAR), soluble cleaved (scuPAR) or soluble spliced (ssuPAR) isoforms.
Results
Elevated expression of uPAR was a feature of cultured HBECs from asthma patients, suggesting intrinsic alterations in asthma patient cells. Soluble uPAR levels inversely correlated with barrier properties of the HBEC layer in 2D and ALI. Blocking uPAR-integrin interactions enhanced barrier formation. The gain of function cells showed limited transcriptomic changes.
Conclusion
This study provides a significant advance in our understanding of the relationship between asthma, uPAR and the epithelial barrier, where elevated circulating uPAR results in a reduced cell barrier, a phenotype prevalent in asthma.
{"title":"Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity","authors":"Michael A. Portelli, Sangita Bhaker, Vincent Pang, David O. Bates, Simon R. Johnson, Andrew P. Mazar, Dominick Shaw, Christopher Brightling, Ian Sayers","doi":"10.1002/clt2.12293","DOIUrl":"https://doi.org/10.1002/clt2.12293","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Expression of the urokinase plasminogen activator receptor (uPAR) is elevated in the airway epithelium in asthma; however, the contribution of uPAR to asthma pathogenesis and scope for therapeutic targeting remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To determine (i) the expression profile of uPAR in cultured human bronchial epithelial cells (HBEC) from asthma patients, (ii) the relationship between uPAR and the epithelial barrier, including blocking uPAR functions and (iii) the function of different uPAR isoforms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>uPAR levels in HBECs isolated from asthma patients and cells at air liquid interface (ALI) during differentiation were quantified. Transepithelial electrical resistance or electrical cell impedance sensing was used to relate uPAR levels to barrier properties, including effects of uPAR blocking antibodies. The functional effects of gain of function was determined using transcriptomics, in cells over-expressing membrane (muPAR), soluble cleaved (scuPAR) or soluble spliced (ssuPAR) isoforms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Elevated expression of uPAR was a feature of cultured HBECs from asthma patients, suggesting intrinsic alterations in asthma patient cells. Soluble uPAR levels inversely correlated with barrier properties of the HBEC layer in 2D and ALI. Blocking uPAR-integrin interactions enhanced barrier formation. The gain of function cells showed limited transcriptomic changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides a significant advance in our understanding of the relationship between asthma, uPAR and the epithelial barrier, where elevated circulating uPAR results in a reduced cell barrier, a phenotype prevalent in asthma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50117353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alessandro Fiocchi, Linda Monaci, Elisabetta De Angelis, Veronica Calandrelli, Lamia Dahdah, Rocco Valluzzi, Sara Urbani, Carmen Mazzuca, Stefania Arasi, Arianna Cafarotti, Carla Riccardi, Maria Cristina Artesani, Lorenza Putignani, Valentina Pecora, Valeria Marzano, Vincenzo Fierro
Background
The frequency and severity of reactions in food-allergic consumers exposed to unintentional food allergen contamination during production is unknown. To warn allergic consumers, it has been suggested for pre-packaged foods to be precautionary labelled when the food allergen contamination may exceed the amount to which 1%–5% of the population could react (ED01–ED05). ED01 for hazelnut and milk have been estimated at 0.1 and 0.2 mg, respectively, by the Voluntary Incidental Trace Allergen Labelling (VITAL) initiative. The respective reference doses recommended by the FAO/WHO Codex consultation are 3 and 2 mg. We evaluated the reactivity to potential traces of milk and hazelnut allergens in allergen-free pre-packaged products by children affected by severe allergies to milk and hazelnuts.
Methods
Oral Food Challenges with commercially available hazelnut-free wafer biscuits and milk-free chocolate pralines were administered to patients with severe food allergies to hazelnut and cow's milk, respectively. Contamination levels of milk or hazelnut allergens were measured using chromatographic separation interfaced with triple quadrupole mass spectrometry.
Results
No hazelnut allergic patient showed allergic reactions to exposure to biscuits, nor any milk allergic patient displayed allergic reactions to the dark chocolate praline. While no hazelnut trace was detected in biscuits, the praline was found to be contaminated by milk at concentrations ranging between 8 and 35 mg total protein/kg food. In our dose model, these amounts exceeded 1.5–10 times the VITAL ED01 and reached the threshold suggested by the FAO/WHO Codex consultation.
Conclusions
Upon the consumption of food products available on the market, many patients with severe food allergies tolerate significantly higher doses of allergen than reference doses indicated in the VITAL system used for precautionary allergen labelling. These doses support the safety of the FAO/WHO recommended reference doses.
{"title":"Reactivity to allergenic food contaminants: A study on products on the market","authors":"Alessandro Fiocchi, Linda Monaci, Elisabetta De Angelis, Veronica Calandrelli, Lamia Dahdah, Rocco Valluzzi, Sara Urbani, Carmen Mazzuca, Stefania Arasi, Arianna Cafarotti, Carla Riccardi, Maria Cristina Artesani, Lorenza Putignani, Valentina Pecora, Valeria Marzano, Vincenzo Fierro","doi":"10.1002/clt2.12301","DOIUrl":"10.1002/clt2.12301","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The frequency and severity of reactions in food-allergic consumers exposed to unintentional food allergen contamination during production is unknown. To warn allergic consumers, it has been suggested for pre-packaged foods to be precautionary labelled when the food allergen contamination may exceed the amount to which 1%–5% of the population could react (ED01–ED05). ED01 for hazelnut and milk have been estimated at 0.1 and 0.2 mg, respectively, by the Voluntary Incidental Trace Allergen Labelling (VITAL) initiative. The respective reference doses recommended by the FAO/WHO Codex consultation are 3 and 2 mg. We evaluated the reactivity to potential traces of milk and hazelnut allergens in allergen-free pre-packaged products by children affected by severe allergies to milk and hazelnuts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Oral Food Challenges with commercially available hazelnut-free wafer biscuits and milk-free chocolate pralines were administered to patients with severe food allergies to hazelnut and cow's milk, respectively. Contamination levels of milk or hazelnut allergens were measured using chromatographic separation interfaced with triple quadrupole mass spectrometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No hazelnut allergic patient showed allergic reactions to exposure to biscuits, nor any milk allergic patient displayed allergic reactions to the dark chocolate praline. While no hazelnut trace was detected in biscuits, the praline was found to be contaminated by milk at concentrations ranging between 8 and 35 mg total protein/kg food. In our dose model, these amounts exceeded 1.5–10 times the VITAL ED01 and reached the threshold suggested by the FAO/WHO Codex consultation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Upon the consumption of food products available on the market, many patients with severe food allergies tolerate significantly higher doses of allergen than reference doses indicated in the VITAL system used for precautionary allergen labelling. These doses support the safety of the FAO/WHO recommended reference doses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 9","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Markus Magerl, Anna Sala-Cunill, Christina Weber-Chrysochoou, Susanne Trainotti, Ilaria Mormile, Giuseppe Spadaro
Hereditary angioedema (HAE) is a rare autosomal dominant disease, with patients often suffering with associated symptoms for many years before receiving a correct diagnosis. The symptoms greatly impact a patient's quality of life (QoL) and include excruciating abdominal pain and angioedema of the skin and submucosa. Angioedema of the larynx represents a significant mortality risk in undiagnosed patients, and a large proportion of patients with HAE receive incorrect diagnoses and undergo unnecessary surgery. HAE-specific treatments can control and prevent acute life-threatening episodes, in addition to improving QoL, emphasizing the value of early diagnosis for patients. Diagnostic delay may be due to a lack of HAE awareness by healthcare professionals and the similarity of HAE symptoms with those of more common conditions, complicating differential diagnosis. The multifaceted nature of the condition may result in visits to one of many different medical settings, for example: the Emergency Room, pediatrics, general practice, otolaryngology, gastroenterology, and dermatology. Therefore, it is crucial that physicians in multiple healthcare specialties are aware of the disease to ensure that patients with HAE receive a timely diagnosis. Using patient cases from various medical specialties, this review highlights the necessity for cross-specialty awareness of HAE and outlines the essential information for the various healthcare professionals that may encounter a patient with HAE symptoms, in order to effectively treat and/or diagnose HAE.
{"title":"Could it be hereditary angioedema?—Perspectives from different medical specialties","authors":"Markus Magerl, Anna Sala-Cunill, Christina Weber-Chrysochoou, Susanne Trainotti, Ilaria Mormile, Giuseppe Spadaro","doi":"10.1002/clt2.12297","DOIUrl":"10.1002/clt2.12297","url":null,"abstract":"<p>Hereditary angioedema (HAE) is a rare autosomal dominant disease, with patients often suffering with associated symptoms for many years before receiving a correct diagnosis. The symptoms greatly impact a patient's quality of life (QoL) and include excruciating abdominal pain and angioedema of the skin and submucosa. Angioedema of the larynx represents a significant mortality risk in undiagnosed patients, and a large proportion of patients with HAE receive incorrect diagnoses and undergo unnecessary surgery. HAE-specific treatments can control and prevent acute life-threatening episodes, in addition to improving QoL, emphasizing the value of early diagnosis for patients. Diagnostic delay may be due to a lack of HAE awareness by healthcare professionals and the similarity of HAE symptoms with those of more common conditions, complicating differential diagnosis. The multifaceted nature of the condition may result in visits to one of many different medical settings, for example: the Emergency Room, pediatrics, general practice, otolaryngology, gastroenterology, and dermatology. Therefore, it is crucial that physicians in multiple healthcare specialties are aware of the disease to ensure that patients with HAE receive a timely diagnosis. Using patient cases from various medical specialties, this review highlights the necessity for cross-specialty awareness of HAE and outlines the essential information for the various healthcare professionals that may encounter a patient with HAE symptoms, in order to effectively treat and/or diagnose HAE.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 9","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41112741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Torsten Zuberbier, Amir Abdul Latiff, Xenofon Aggelidis, Matthias Augustin, Radu-Gheorghe Balan, Christine Bangert, Lisa Beck, Thomas Bieber, Jonathan A. Bernstein, Marta Bertolin Colilla, Alejandro Berardi, Anna Bedbrook, Carsten Bindslev-Jensen, Jean Bousquet, Marjolein de Bruin-Weller, Dayanne Bruscky, Betul Buyuktiryaki, Giorgio Walter Canonica, Carla Castro, Natia Chanturidze, Herberto Jose Chong-Neto, Chia-Yu Chu, Leena Chularojanamontri, Michael Cork, Roberta F. J. Criado, Laia Curto Barredo, Adnan Custovic, Ulf Darsow, Arben Emurlai, Ana de Pablo, Stefano Del Giacco, Giampiero Girolomoni, Tanja Deleva Jovanova, Mette Deleuran, Nikolaos Douladiris, Bruno Duarte, Ruta Dubakiene, Esben Eller, Batya Engel-Yeger, Luis Felipe Ensina, Nelson Rosario Filho, Carsten Flohr, Daria Fomina, Wojciech Francuzik, Maria Laura Galimberti, Ana M. Giménez-Arnau, Kiran Godse, Charlotte Gotthard Mortz, Maia Gotua, Michihiro Hide, Wolfram Hoetzenecker, Nicolas Hunzelmann, Alan Irvine, Carolyn Jack, Ioanna Kanavarou, Norito Katoh, Tamar Kinaciyan, Emek Kocatürk, Kanokvalai Kulthanan, Hilde Lapeere, Susanne Lau, Mariana Machado Forti Nastri, Michael Makris, Eli Mansour, Alexander Marsland, Mara Morelo Rocha Felix, Ana Paula Moschione Castro, Eustachio Nettis, J. F. Nicolas, Audrey Nosbaum, Mikaela Odemyr, Niki Papapostolou, Claudio A. S. Parisi, Sushil Paudel, Jonny Peter, Prakash Pokharel, Luis Puig, Tamara Quint, German Dario Ramon, Frederico Regateiro, Giampaolo Ricci, Cristine Rosario, Cansin Sackesen, Peter Schmid-Grendelmeier, Esther Serra-Baldrich, Kristina Siemens, Cathrine Smith, Petra Staubach, Katarina Stevanovic, Özlem Su-Kücük, Gordon Sussman, Simona Tavecchio, Natasa Teovska Mitrevska, Diamant Thaci, Elias Toubi, Claudia Traidl-Hoffmann, Regina Treudler, Zahava Vadasz, Ingrid van Hofman, Maria Teresa Ventura, Zhao Wang, Thomas Werfel, Andreas Wollenberg, Ariana Yang, Yik Weng Yew, Zuotao Zhao, Ricardo Zwiener, Margitta Worm
Introduction
The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems.
Methods
The GA2LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2EN ADCARE centres.
Results
The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD.
Conclusion
The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.
{"title":"A concept for integrated care pathways for atopic dermatitis—A GA2LEN ADCARE initiative","authors":"Torsten Zuberbier, Amir Abdul Latiff, Xenofon Aggelidis, Matthias Augustin, Radu-Gheorghe Balan, Christine Bangert, Lisa Beck, Thomas Bieber, Jonathan A. Bernstein, Marta Bertolin Colilla, Alejandro Berardi, Anna Bedbrook, Carsten Bindslev-Jensen, Jean Bousquet, Marjolein de Bruin-Weller, Dayanne Bruscky, Betul Buyuktiryaki, Giorgio Walter Canonica, Carla Castro, Natia Chanturidze, Herberto Jose Chong-Neto, Chia-Yu Chu, Leena Chularojanamontri, Michael Cork, Roberta F. J. Criado, Laia Curto Barredo, Adnan Custovic, Ulf Darsow, Arben Emurlai, Ana de Pablo, Stefano Del Giacco, Giampiero Girolomoni, Tanja Deleva Jovanova, Mette Deleuran, Nikolaos Douladiris, Bruno Duarte, Ruta Dubakiene, Esben Eller, Batya Engel-Yeger, Luis Felipe Ensina, Nelson Rosario Filho, Carsten Flohr, Daria Fomina, Wojciech Francuzik, Maria Laura Galimberti, Ana M. Giménez-Arnau, Kiran Godse, Charlotte Gotthard Mortz, Maia Gotua, Michihiro Hide, Wolfram Hoetzenecker, Nicolas Hunzelmann, Alan Irvine, Carolyn Jack, Ioanna Kanavarou, Norito Katoh, Tamar Kinaciyan, Emek Kocatürk, Kanokvalai Kulthanan, Hilde Lapeere, Susanne Lau, Mariana Machado Forti Nastri, Michael Makris, Eli Mansour, Alexander Marsland, Mara Morelo Rocha Felix, Ana Paula Moschione Castro, Eustachio Nettis, J. F. Nicolas, Audrey Nosbaum, Mikaela Odemyr, Niki Papapostolou, Claudio A. S. Parisi, Sushil Paudel, Jonny Peter, Prakash Pokharel, Luis Puig, Tamara Quint, German Dario Ramon, Frederico Regateiro, Giampaolo Ricci, Cristine Rosario, Cansin Sackesen, Peter Schmid-Grendelmeier, Esther Serra-Baldrich, Kristina Siemens, Cathrine Smith, Petra Staubach, Katarina Stevanovic, Özlem Su-Kücük, Gordon Sussman, Simona Tavecchio, Natasa Teovska Mitrevska, Diamant Thaci, Elias Toubi, Claudia Traidl-Hoffmann, Regina Treudler, Zahava Vadasz, Ingrid van Hofman, Maria Teresa Ventura, Zhao Wang, Thomas Werfel, Andreas Wollenberg, Ariana Yang, Yik Weng Yew, Zuotao Zhao, Ricardo Zwiener, Margitta Worm","doi":"10.1002/clt2.12299","DOIUrl":"https://doi.org/10.1002/clt2.12299","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The GA<sup>2</sup>LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL<sup>2</sup>EN ADCARE centres.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 9","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50150900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcus Maurer, Thomas Buttgereit, Markus Magerl, Kathrin Schön, Zsusanna Balla, Henriette Farkas
Background
The coronavirus disease pandemic and its containing measures have caused concerns for patients with hereditary angioedema (HAE) and their treating physicians. Both faced challenges surrounding interaction, and communication had to adapt to facilitate appropriate management. Specifically, the pandemic resulted in reduced in-person contact in clinics. Where possible, telemedicine appointments were offered and treatment outside the hospital setting was encouraged.
Body
The pandemic markedly affected patient-physician communication, which is essential to maintain partnerships and optimize care. Although patients with HAE are often experts in their condition, guidance by their physicians is essential, especially with the recent shift toward patient-centered management for rare diseases and shared decision-making (SDM). SDM enables patients to take control of their disease and allows the risks and benefits of treatment to be discussed with their physicians. This review explores perspectives from patients and physicians in the HAE clinical setting, particularly regarding their experiences with communication throughout the pandemic. We discuss the importance of SDM in rare diseases such as HAE, factors that impact effective communication, and potential solutions.
Conclusion
Since patient-centered care and SDM have particular relevance in rare diseases in general, we believe our findings could be transferrable and applicable in the management of other rare diseases.
{"title":"Patient-physician interactions in hereditary angioedema—Key learnings from the coronavirus disease 2019 pandemic","authors":"Marcus Maurer, Thomas Buttgereit, Markus Magerl, Kathrin Schön, Zsusanna Balla, Henriette Farkas","doi":"10.1002/clt2.12300","DOIUrl":"10.1002/clt2.12300","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The coronavirus disease pandemic and its containing measures have caused concerns for patients with hereditary angioedema (HAE) and their treating physicians. Both faced challenges surrounding interaction, and communication had to adapt to facilitate appropriate management. Specifically, the pandemic resulted in reduced in-person contact in clinics. Where possible, telemedicine appointments were offered and treatment outside the hospital setting was encouraged.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Body</h3>\u0000 \u0000 <p>The pandemic markedly affected patient-physician communication, which is essential to maintain partnerships and optimize care. Although patients with HAE are often experts in their condition, guidance by their physicians is essential, especially with the recent shift toward patient-centered management for rare diseases and shared decision-making (SDM). SDM enables patients to take control of their disease and allows the risks and benefits of treatment to be discussed with their physicians. This review explores perspectives from patients and physicians in the HAE clinical setting, particularly regarding their experiences with communication throughout the pandemic. We discuss the importance of SDM in rare diseases such as HAE, factors that impact effective communication, and potential solutions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Since patient-centered care and SDM have particular relevance in rare diseases in general, we believe our findings could be transferrable and applicable in the management of other rare diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 9","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rebecca Czolk, Maria Ruiz-Castell, Oliver Hunewald, Naphisabet Wanniang, Gwenaëlle Le Coroller, Christiane Hilger, Michel Vaillant, Guy Fagherazzi, Françoise Morel-Codreanu, Markus Ollert, Annette Kuehn
Background
Even though the prevalence of allergies is increasing, population-based data are still scarce. As a read-out for chronic inflammatory information, new methods are needed to integrate individual biological measurements and lifestyle parameters to mitigate the consequences and costs of allergic burden for society.
Methods
More than 480.000 data points were collected from 1462 Luxembourg adults during the representative, cross-sectional European Health Examination Survey, spanning health and lifestyle reports. Deep IgE-profiles based on unsupervised clustering were correlated with data of the health survey.
Findings
42.6% of the participants reported a physician-diagnosed allergy and 44% were found to be IgE-positive to at least one allergen or extract. The main sensitization sources were tree pollens followed by grass pollens and mites (52.4%, 51.8% and 40.3% of sensitized participants respectively), suggesting seasonal as well as perennial burden. The youngest group of participants (25–34 years old) showed the highest burden of sensitization, with 18.2% of them having IgE to 10 or more allergen groups. Unsupervised clustering revealed that the biggest cluster of 24.4% of participants was also the one with the highest medical need, marked by their multi-sensitization to respiratory sources.
Interpretation
Our novel approach to analyzing large biosample datasets together with health information allows the measurement of the chronic inflammatory disease burden in the general population and led to the identification of the most vulnerable groups in need of better medical care.
{"title":"Novel, computational IgE-clustering in a population-based cross-sectional study: Mapping the allergy burden","authors":"Rebecca Czolk, Maria Ruiz-Castell, Oliver Hunewald, Naphisabet Wanniang, Gwenaëlle Le Coroller, Christiane Hilger, Michel Vaillant, Guy Fagherazzi, Françoise Morel-Codreanu, Markus Ollert, Annette Kuehn","doi":"10.1002/clt2.12292","DOIUrl":"10.1002/clt2.12292","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Even though the prevalence of allergies is increasing, population-based data are still scarce. As a read-out for chronic inflammatory information, new methods are needed to integrate individual biological measurements and lifestyle parameters to mitigate the consequences and costs of allergic burden for society.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>More than 480.000 data points were collected from 1462 Luxembourg adults during the representative, cross-sectional European Health Examination Survey, spanning health and lifestyle reports. Deep IgE-profiles based on unsupervised clustering were correlated with data of the health survey.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>42.6% of the participants reported a physician-diagnosed allergy and 44% were found to be IgE-positive to at least one allergen or extract. The main sensitization sources were tree pollens followed by grass pollens and mites (52.4%, 51.8% and 40.3% of sensitized participants respectively), suggesting seasonal as well as perennial burden. The youngest group of participants (25–34 years old) showed the highest burden of sensitization, with 18.2% of them having IgE to 10 or more allergen groups. Unsupervised clustering revealed that the biggest cluster of 24.4% of participants was also the one with the highest medical need, marked by their multi-sensitization to respiratory sources.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our novel approach to analyzing large biosample datasets together with health information allows the measurement of the chronic inflammatory disease burden in the general population and led to the identification of the most vulnerable groups in need of better medical care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 9","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41121299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Danny M. Cohn, Emel Aygören-Pürsün, Jonathan A. Bernstein, Henriette Farkas, William R. Lumry, Marcus Maurer, Andrea Zanichelli, Matthew Iverson, James Hao, Michael D. Smith, Christopher M. Yea, Paul K. Audhya, Marc A. Riedl
Background
Hereditary angioedema (HAE) with C1-inhibitor deficiency (HAE-C1-INH) is characterized by recurrent, debilitating episodes of swelling. Sebetralstat, an investigational oral plasma kallikrein inhibitor, demonstrated promising efficacy for on-demand treatment of HAE-C1-INH in a phase 2 trial. We describe the multipronged approach informing the design of KONFIDENT, a phase 3 randomized, placebo-controlled, three-way crossover trial evaluating the efficacy and safety of sebetralstat in patients aged ≥12 years with HAE-C1-INH.
Methods
To determine an optimal endpoint to measure the beginning of symptom relief in KONFIDENT, we engaged patients with HAE on clinical outcome measures and subsequently conducted analyses of phase 2 outcomes. Sample size was determined via a simulation-based approach using phase 2 data.
Results
Patient interviews revealed a strong preference (71%) for the Patient Global Impression of Change (PGI-C) over other measures and indicated a rating of “A Little Better” as a clinically meaningful milestone. In phase 2, a rating of “A Little Better” demonstrated agreement with attack severity improvement and resolution on the Patient Global Impression of Severity and had better sensitivity than “Better.” Simulations indicated that 84 patients completing treatment would ensure at least 90% power for assessing the primary endpoint of time to beginning of symptom relief defined as a PGI-C rating of at least “A Little Better” for two time points in a row.
Conclusions
Patient feedback and phase 2 data support PGI-C as the primary outcome measure in the phase 3 KONFIDENT trial evaluating sebetralstat, which has the potential to be the first oral on-demand treatment for HAE-C1-INH attacks.
{"title":"Evaluation of patient-reported outcome measures for on-demand treatment of hereditary angioedema attacks and design of KONFIDENT, a phase 3 trial of sebetralstat","authors":"Danny M. Cohn, Emel Aygören-Pürsün, Jonathan A. Bernstein, Henriette Farkas, William R. Lumry, Marcus Maurer, Andrea Zanichelli, Matthew Iverson, James Hao, Michael D. Smith, Christopher M. Yea, Paul K. Audhya, Marc A. Riedl","doi":"10.1002/clt2.12288","DOIUrl":"10.1002/clt2.12288","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary angioedema (HAE) with C1-inhibitor deficiency (HAE-C1-INH) is characterized by recurrent, debilitating episodes of swelling. Sebetralstat, an investigational oral plasma kallikrein inhibitor, demonstrated promising efficacy for on-demand treatment of HAE-C1-INH in a phase 2 trial. We describe the multipronged approach informing the design of KONFIDENT, a phase 3 randomized, placebo-controlled, three-way crossover trial evaluating the efficacy and safety of sebetralstat in patients aged ≥12 years with HAE-C1-INH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To determine an optimal endpoint to measure the beginning of symptom relief in KONFIDENT, we engaged patients with HAE on clinical outcome measures and subsequently conducted analyses of phase 2 outcomes. Sample size was determined via a simulation-based approach using phase 2 data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patient interviews revealed a strong preference (71%) for the Patient Global Impression of Change (PGI-C) over other measures and indicated a rating of “A Little Better” as a clinically meaningful milestone. In phase 2, a rating of “A Little Better” demonstrated agreement with attack severity improvement and resolution on the Patient Global Impression of Severity and had better sensitivity than “Better.” Simulations indicated that 84 patients completing treatment would ensure at least 90% power for assessing the primary endpoint of time to beginning of symptom relief defined as a PGI-C rating of at least “A Little Better” for two time points in a row.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patient feedback and phase 2 data support PGI-C as the primary outcome measure in the phase 3 KONFIDENT trial evaluating sebetralstat, which has the potential to be the first oral on-demand treatment for HAE-C1-INH attacks.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"13 9","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41113646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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